Cancer Cell Permeability Induced by Tumor Treating Fields (TTFields) as a Physical Approach to Improve Chemotherapy Uptake and Overcome Multidrug Resistance

多重耐药 癌症 化疗 磁导率 癌症研究 医学 药理学 抗药性 化学 生物 内科学 微生物学 生物化学
作者
Bella Koltun,Tali Voloshin,Cfir David,Tal Kan,Yiftah Barsheshet,Alexandra Volodin,Shay Cahal,Catherine Tempel-Brami,Mai Shai,Sara Jacobovitch,David Roash-Lancry,Boris Brant,Noa Kaynan,Lilach Koren,Anat Klein-Goldberg,Efrat Zemer Tov,Rom Paz,Adi Haber,Moshe Giladi,Uri Weinberg
出处
期刊:Molecular Cancer Therapeutics [American Association for Cancer Research]
卷期号:24 (11): 1815-1825 被引量:1
标识
DOI:10.1158/1535-7163.mct-25-0019
摘要

Abstract Multidrug resistance (MDR) is a major challenge in cancer treatment. One predominant MDR mechanism involves the overexpression of ATP-binding cassette transporter proteins on the cell membrane, leading to increased chemotherapy efflux. Strategies to resolve MDR have not yet yielded substantial survival benefits. Tumor Treating Fields (TTField) represent an innovative therapeutic modality for cancer treatment and have been shown to enhance membrane permeability in glioblastoma cells. The current study aimed to characterize this phenomenon and evaluate its potential to increase chemotherapy accumulation, thus overcoming MDR. In vitro analyses using the exclusion dye 7-aminoactinomycin D demonstrated that TTFields-induced enhancement of membrane permeability is pan-cancer while specific to cancer cells, reversible, and requires cell-cycle progression through the G2–M phase. Furthermore, TTFields significantly increased intracellular accumulation of doxorubicin (DOX), mitoxantrone, and cisplatin in resistant cells, restoring uptake to levels observed in sensitive cells, without altering MDR transporter expression. Increased chemotherapy accumulation was confirmed in vivo as demonstrated by elevated DOX accumulation in breast tumors and increased paclitaxel accumulation in lung tumors. Importantly, TTFields sensitized both DOX-sensitive and DOX-resistant cells to DOX-induced cytotoxicity in vitro. In mouse models bearing breast tumors, co-administration of therapeutic or sub-therapeutic DOX doses together with TTFields significantly reduced tumor growth compared with either treatment alone. In conclusion, the findings suggest that adding TTFields to chemotherapy regimens may enhance drug delivery and efficacy in tumors exhibiting MDR. Further clinical studies evaluating TTFields concomitant with chemotherapy in patients with MDR cancer are warranted.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
鹅鹅鹅丶完成签到,获得积分10
刚刚
张佳军发布了新的文献求助10
刚刚
a面完成签到 ,获得积分10
刚刚
刚刚
1秒前
鬼笔环肽发布了新的文献求助10
1秒前
小n完成签到,获得积分10
2秒前
wujin完成签到,获得积分10
2秒前
wgl200212完成签到,获得积分10
3秒前
孤独的鹰完成签到,获得积分10
4秒前
小欧医生完成签到,获得积分10
4秒前
Ton汤发布了新的文献求助10
4秒前
4秒前
zhanglongquan发布了新的文献求助10
4秒前
4秒前
FashionBoy应助小薇采纳,获得20
4秒前
5秒前
魏芸芸发布了新的文献求助10
5秒前
5秒前
lawang完成签到,获得积分10
5秒前
绝世冰淇淋完成签到 ,获得积分10
6秒前
6秒前
庾烙发布了新的文献求助10
6秒前
852应助LS采纳,获得10
6秒前
7秒前
utopia发布了新的文献求助10
7秒前
myg123完成签到 ,获得积分10
8秒前
索莫完成签到,获得积分10
8秒前
ding应助qq采纳,获得10
8秒前
白昼潜行完成签到,获得积分10
8秒前
小刘完成签到,获得积分10
9秒前
9秒前
小杨完成签到,获得积分10
9秒前
wujin发布了新的文献求助10
10秒前
北陌完成签到 ,获得积分10
10秒前
10秒前
天天快乐应助fogsea采纳,获得10
10秒前
yy发布了新的文献求助10
11秒前
wlei发布了新的文献求助10
11秒前
Yuhaoo完成签到 ,获得积分10
11秒前
高分求助中
晶体学对称群—如何读懂和应用国际晶体学表 1500
Problem based learning 1000
Constitutional and Administrative Law 1000
Microbially Influenced Corrosion of Materials 500
Die Fliegen der Palaearktischen Region. Familie 64 g: Larvaevorinae (Tachininae). 1975 500
Numerical controlled progressive forming as dieless forming 400
Rural Geographies People, Place and the Countryside 400
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 纳米技术 计算机科学 内科学 化学工程 复合材料 物理化学 基因 遗传学 催化作用 冶金 量子力学 光电子学
热门帖子
关注 科研通微信公众号,转发送积分 5388329
求助须知:如何正确求助?哪些是违规求助? 4510410
关于积分的说明 14035256
捐赠科研通 4421211
什么是DOI,文献DOI怎么找? 2428689
邀请新用户注册赠送积分活动 1421302
关于科研通互助平台的介绍 1400553